The present invention relates to methods for accelerating non-surgical corneal reshaping involving the release of corneal hardening agents which facilitate reshaping of the cornea to correct refractive errors of the eye.
The cornea is the clear dome on the front of the eye. About eighty percent of the focus, or refracting, power of the eye is at the cornea. When the cornea is misshapen or the axial length of the eye is too long or too short, or when the lens of the eye is functioning abnormally, the refractive errors of myopias (nearsightedness), astigmatism (blurred vision) or hyperopia (farsightedness) can result. Throughout history, mankind has experimented with ways to improve vision. Although these ways have provided many people with a reasonable quality of life, they still have limitations.
Glasses correct refractive errors of the eye by changing the angle at which the light enters the cornea by refracting the light with a lens before it reaches the cornea. But for many lifestyles, glasses are very inconvenient. And for some people, they do not give the quality of vision desired. When the glasses are taken off, the refractive error still exists. Contact lenses correct refractive errors of the eye by replacing the defective corneal curve with the front curve of a contact lens that is calculated to render the eye emmetropic, which is a state where no visual correction is necessary. But wearing contact lens also has a price. The wearer must spend considerable time and money both in the maintenance and the application of the contacts. There still remains a limitation as to the types of activities in which one can participate. And, lastly, long term lens wearers may develop an intolerance to wearing their lenses as well as long term damage. When the lens is removed, the refractive error still remains.
Radial Keratotomy (xe2x80x9cRKxe2x80x9d) is a surgical operation to improve myopia by changing the curve of the cornea over the pupil. The surgeon makes several deep incisions in the cornea in a radial or spoke-like pattern. The incisions are intended to flatten out the central cornea to correct the patient""s vision. However, RK can only be used to correct low amounts of myopia. It cannot address the problems of hyperopia. The main drawback is that the cornea is seriously weakened and frequently continues to change shape with time. A newer type of RK that involves making shorter incisions is replacing standard RK. But newer techniques using computerized assessment, precisely calculated cutting patterns, and lasers will probably result in the rapid decline of RK.
Photorefractive Keratectomy (xe2x80x9cPRKxe2x80x9d) is a surgical procedure similar to RK involving the use of an excimer laser, which is controlled by a computer that measures the shape of the eye and sets the power of the laser. With the PRK process, the excimer laser permits the ability to sculpt rather than cut the surface of the cornea. There are a combination of laser machines that with a combination of computer controls can reliably treat myopia, hyperopia, and astigmatism. However, since PRK is a surgical procedure, it can result in complications. Infection is the most serious complication. Other possible problems include delayed surface healing, corneal haze or scarring, over or undercorrection, and the development of astigmatism. Some individuals can have a poor or excessive healing response. The complications must be treated with medications or further surgery.
Laser in-situ keratomileusis (xe2x80x9cLASIKxe2x80x9d) is a surgical procedure that is a variation on PRK involving an excimer laser and a precise cutting machine called a microkeratome. An ophthalmologist uses the microkeratome to form a circular flap on the cornea. The flap is flipped back, as if on a hinge, to expose the inner layers of the cornea. With the flap folded back, the doctor now makes the refractive correction on the inner layers of the cornea using the excimer laser. Finally, the flap is repositioned to complete the procedure. With a precision laser treatment and normal reattachment and healing of the flap, the refractive results can be rapid and superb. There is, however, a very significant list of potential complications and risks including failure of the microkeratome to leave a hinge on the corneal flap with the first incision, loss of the corneal flap during the operation, loss of the corneal flap after the operation, slipping of the flap and healing off center, first incision too deep or too shallow, invasion of the surface tissue into the central tissue of the cornea, infection of the cornea, loss of visual acuity from scarring or optical distortion due to the flap not being repositioned correctly, technical problems with complex and finicky automated cutting devices, and the procedure being much more dependent upon the surgeon""s operating skills than the computerized precision of the procedure.
Thermokeratoplasty is another corneal reshaping method. In thermokeratoplasty heat is applied to the cornea to induce shrinkage. Corneal stromal collagen shrinks when heated to a temperature of 55xc2x0 C. to 58xc2x0 C., without the destruction of the tissue. If the pattern of shrinkage is properly selected the resulting change in the stress field and mechanical properties caused by the shrunken collagen fibers can be used to reshape the cornea.
A variety of methods are known with which to practice thermokeratoplasty. For example, U.S. Pat. No. 4,881,543 discloses one method and apparatus for heating the central stroma of the cornea with microwave electromagnetic energy to the shrinking temperature of the collagen while circulating a cool fluid over the anterior surface of the cornea. In another example, U.S. Pat. No. 5,779,696 describes the use of light energy to reshape the cornea in a process known as photothermokeratoplasty. All of the processes suffer from a variety of shortcomings, including a common flaw in which corneas in the treated subjects are unstable after the thermokeratoplasty procedure is concluded.
Orthokeratology is a non-surgical procedure designed to correct refractive errors by reshaping the cornea to the curvature required for emmetropia. This is accomplished by applying a series of progressive contact lens changes that retrain the eye to achieve a corneal curvature. However, once a desired corneal curvature has been produced, retainer contact lenses must be worn to stabilize the results or regression may occur.
Enzyme Orthokeratology is related to traditional Orthokeratology in that it is defined primarily as a contact lens procedure of correcting refractive errors by reshaping the cornea to the curvature required for emmetropia. The program is supplemented by chemically softening the cornea. By supplying drugs that soften the cornea, the cornea is chemically reshaped by being molded to the concave surface of a contact lens having a predetermined curvature. The contact lens radius is selected to render the eye emmetropic. Retainer contact lenses will not be required for good visual acuity after removal of the contact lens from the cornea and regression will not be a problem. However, the length of program of treatment varies from weeks to months with progressive contact lens changes and periodic follow-up examinations.
Notwithstanding the foregoing, there remains a need for non-surgical methods of correcting refractive errors of the eye which can correct various degrees of refractive error and produce relatively permanent results in a much shorter period of time.
An Enzyme Orthokeratology method is provided for correcting refractive errors in the eye of a subject mammal. Accelerating reshaping of the cornea is accomplished by administering a corneal hardening amount of a corneal hardening agent to the eye of the subject. Reformation is accomplished under the influence of a rigid contact lens or a series of lenses having a concave curvature that will correct a refractive error. The cornea rapidly reshapes its convex curvature to the concave curvature of the contact lens, rendering the eye emmetropic. The cornea is permitted to xe2x80x9chardenxe2x80x9d to retain the new emmetropic shape. After xe2x80x9chardeningxe2x80x9d has occurred, the lens rendering the eye emmetropic is removed.
A method for correcting refractive errors in an eye of a subject mammal, comprising the steps of selecting a pharmaceutically acceptable corneal hardening agent on the basis of its being able to harden the cornea in the eye of the subject without causing damage to the cornea, administering to the eye of the subject a corneal hardening amount of the agent so that the cornea can be reshaped from a first configuration to a desired second configuration, fitting the cornea with a rigid contact lens having a concave curvature of the desired second configuration, permitting the cornea to reshape to the desired second configuration under the influence of the lens, and removing the lens when the cornea is capable of maintaining the desired second configuration without the support of the lens.
Preferably, the types of refractive errors are selected from the group consisting of myopia, hyperopia and astigmatism and the corneal hardening agent is a cross linker such as an aldehyde. This aldehyde may be selected from the group consisting,of acetaldehyde, glyceraldehyde, phenylacetaldehyde, valeraldehyde, 3,4-dihydroxyphenylacetaldehyde, mutarotational isomers of aldehydes, ascorbic acid and dehydroascorbic acid. The corneal hardening agent may also be an enzyme, where the enzyme mediates cross linking reactions. Examples of a suitable enzyme include lysyl oxidase or prolyl oxidase. In one embodiment, the corneal hardening agents may be administered by injection into the eye, by topical administration into the eye in the form of eye drops or by means of a contact lens.
In another embodiment, the additional step of administering to the eye a corneal softening amount of a pharmaceutically acceptable corneal softening agent sufficient to soften the cornea of the eye so that the cornea can be reshaped is performed as part of the method to correct a refractive error. In this embodiment, the corneal softening agent is an enzyme that degrades proteoglycans in the cornea, such as hyaluronidase.
Another embodiment of the present invention is a kit for performing refractive corrections in an eye of a subject mammal, comprising: a corneal hardening agent in unit dosage form and a rigid corrective lens having a desired concave structure.
Still another embodiment of the present invention is a reaction mixture comprising: the eye of a subject mammal, a corneal hardening agent in unit dosage form; and a rigid corrective lens having a desired concave structure.
Yet another embodiment is a method of rehabilitating corneal irregularity and correcting refractive error in an eye of a subject mammal with irregular corneal shape, comprising the steps of: identifying a subject with irregular corneal shape, selecting a pharmaceutically acceptable corneal hardening agent on the basis of its being able to harden the cornea in the eye of the subject without causing damage to the cornea, administering to the eye of the subject a corneal hardening amount of the agent so that the cornea can be reshaped from a first configuration to a desired second configuration, fitting the cornea with a rigid contact lens having a concave curvature of the desired second configuration, permitting the cornea to reshape to the desired second configuration under the influence of the lens, and removing the lens when the cornea is capable of maintaining the desired second configuration without the support of the lens. Subjects may be identified for this procedure by diagnosing them as having a condition selected from the group consisting of: keratoconus, contact lens induced corneal warpage, contact lens intolerance, corneal ulcers, corneal melting disorders, recurrent corneal erosions, pterygium, and irregular corneal shape or uncorrected refractive error due to corneal surgery.
Another embodiment of the present invention is a method for improving the clinical success of surgery to the eye involving the manipulation of a cornea of a subject mammal, comprising the steps of: identifying a subject who has undergone a corneal manipulation, selecting a pharmaceutically acceptable corneal hardening agent on the basis of its being able to harden the cornea in the eye of the subject without causing damage to the cornea, administering to the eye of the subject a corneal hardening amount of the agent so that the cornea can be reshaped from a first configuration to a desired second configuration, fitting the cornea with a rigid contact lens having a concave curvature of the desired second configuration, permitting the cornea to reshape to the desired second configuration under the influence of the lens, and removing the lens when the cornea is capable of maintaining the desired second configuration without the support of the lens. In this embodiment, the typical corneal manipulations are selected from the group consisting of radial keratotomy, photorefractive keratectomy, LASIK, thermokeratoplasty, corneal transplant surgery, cataract surgery, and corneal reshaping by laser.